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JAMA Aug 1992To evaluate the effects of high doses of atropine in children accidentally injected with automatic atropine injectors. These were distributed in Israel during the...
OBJECTIVE
To evaluate the effects of high doses of atropine in children accidentally injected with automatic atropine injectors. These were distributed in Israel during the Persian Gulf Crisis as an antidote for chemical warfare agents.
DESIGN AND SETTING
A national survey in pediatric emergency departments in Israel, involving 22 medical centers, with prospective data collection in 14 centers.
PATIENTS
Children (n = 268) presenting to emergency departments following misuse of automatic atropine injectors.
MAIN OUTCOME MEASURES
Documentation of atropine dose and clinical manifestations; determination of a clinical severity score and its correlation with atropine dose; measurements of serum atropine levels in six patients.
RESULTS
Over a period of 4 months, 268 cases were reported, of which 240 were clinically evaluated. The most common site of injection (75%) was the finger or palm. Doses were up to 17-fold higher than standard doses for age. In 116 children (48%), systemic effects of atropine were observed, and 20 (8%) had severe atropinization. Seizures and life-threatening arrhythmias were not reported, and there were no fatalities. The severity of atropinization was correlated with the dose following a classic nonlinear, dose-response relationship. Serum atropine levels (6.2 to 61.0 ng/mL) were much higher than those observed after administration of therapeutic doses.
CONCLUSIONS
The high incidence of injection in the hand implies accidental use of automatic atropine injectors among children. The lack of mortality or life-threatening complications from injection of large doses of atropine attests to its relative safety in children. The low risk from atropine injections weighed against expected benefit as a lifesaving antidote justifies the distribution of personal atropine injectors to children at risk of organophosphorus nerve agent attack.
Topics: Accidents; Adolescent; Atropine; Child; Child, Preschool; Female; Humans; Israel; Male; Middle East; Prospective Studies; Regression Analysis; Warfare
PubMed: 1629992
DOI: No ID Found -
Chembiochem : a European Journal of... Apr 2021The tropane alkaloids (TAs) hyoscyamine and scopolamine function as acetylcholine receptor antagonists and are used clinically as parasympatholytics to treat... (Review)
Review
The tropane alkaloids (TAs) hyoscyamine and scopolamine function as acetylcholine receptor antagonists and are used clinically as parasympatholytics to treat neuromuscular disorders in humans. While TAs are synthesized in a small subset of plant families, these specialized metabolites are only accumulated in limited quantities in plant organs. The complex chemical structures of these compounds make their industrial production by chemical synthesis very challenging, Therefore, the supply of these TAs still relies on intensive farming of Duboisia shrubs in tropical countries. Many adverse factors such as climate fluctuations and pandemics can thus influence annual world production. Based on the landmark microbial production of the antimalarial semi-synthetic artemisinin, the Smolke group recently developed a yeast cell factory capable of de novo synthesizing hyoscyamine and scopolamine, thus paving the way for an alternative production of these compounds.
Topics: Cholinergic Antagonists; Duboisia; Humans; Hyoscyamine; Molecular Structure; Scopolamine
PubMed: 33215811
DOI: 10.1002/cbic.202000757 -
[How is atropine made in belladonna? New findings on the regulation of plant secondary metabolites].Pharmazie in Unserer Zeit Sep 1996
Review
Topics: Atropa belladonna; Atropine; Flavonoids; Plants, Medicinal; Plants, Toxic
PubMed: 8984502
DOI: 10.1002/pauz.19960250507 -
Toxicology Letters Sep 2011Although the importance of atropine in therapy of organophosphate (OP) poisoning is generally recognized, its dosing is a matter of debate. A retrospective analysis of...
Although the importance of atropine in therapy of organophosphate (OP) poisoning is generally recognized, its dosing is a matter of debate. A retrospective analysis of atropine dosing was undertaken in 34 patients who had been enrolled in a clinical study assessing obidoxime effectiveness in OP-poisoning. All patients were severely intoxicated (suicidal attempts) and required artificial ventilation. Atropine was administered routinely by intensive care physicians for life-threatening muscarinic symptoms, with the recommendation to favor low dosage. The pharmacological active enantiomere S-hyoscyamine was determined by a radioreceptor assay. When RBC-AChE activity ranged between 10% and 30%, S-hyoscyamine plasma concentrations of approx. 5 nmol L⁻¹ were sufficient. This concentration could be maintained with about 0.005 mg h⁻¹ kg⁻¹ atropine. Only when RBC-AChE was completely inhibited, therapy of cholinergic crisis required atropine doses up to 0.06 mg h⁻¹ kg⁻¹. Elimination half-life of S-hyoscyamine was 1.5 h, showing occasionally a second slow elimination phase with t(½)=12 h. Malignant arrhythmias were observed in some 10% of our cases, which occurred late and often in the absence of relevant glandular cholinergic signs, when the S-hyoscyamine concentration was below 2.5 nmol L⁻¹. Arrhythmias mostly resolved on reinstitution of atropine.
Topics: Acetylcholinesterase; Aged; Area Under Curve; Atropine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Erythrocytes; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Organophosphate Poisoning; Pesticides; Poisoning; Retrospective Studies; Stereoisomerism; Suicide, Attempted; Treatment Outcome
PubMed: 21771644
DOI: 10.1016/j.toxlet.2011.07.006 -
Ugeskrift For Laeger Aug 1980
Review
Topics: Atropine; Humans; Preanesthetic Medication; Preoperative Care
PubMed: 6996264
DOI: No ID Found -
Archives of Ophthalmology (Chicago,... Jul 1977One cynomolgus and three vervet monkeys were treated topicall twice daily in one eye with 63 microgram of echothiophate iodide and 750 microgram of atropine sulfate. The...
One cynomolgus and three vervet monkeys were treated topicall twice daily in one eye with 63 microgram of echothiophate iodide and 750 microgram of atropine sulfate. The opposite eyes were treated with echothiophate alone. The eyes treated with echothiophate alone all developed posterior and/or anterior subcapsular cataracts within 26 to 66 days. The echothiophate plus atropine-treated cynomolgus eye developed a cataracts of much delayed onset and lesser severity compared to its echothiophate-only-treated fellow. None of the echothiophate plus atropine-treated vervet eyes developed cataracts during the 121 (two eyes) or 231 (one eye) days of treatment. After 121 days of echothiophate plus atropine treatment, two vervet eyes were switched to echothiophate alone. Both eyes developed unequivocal posterior and anterior subcapsular lens opacities, one within 51 and one within 71 days after the switch. We conclude that atropine inhibits echothiophate cataracto-genesis in vervet and cynomolgus monkeys.
Topics: Administration, Topical; Animals; Atropine; Cataract; Chlorocebus aethiops; Echothiophate Iodide; Female; Haplorhini; Macaca fascicularis
PubMed: 406884
DOI: 10.1001/archopht.1977.04450070160017 -
Acta Pharmacologica Et Toxicologica Sep 1980A simple, specific and sensitive radioimmunoassay is described for atropine (dl-hyoscyamine) and l-hyoscyamine. Antiserum was obtained from rabbits immunized with an...
A simple, specific and sensitive radioimmunoassay is described for atropine (dl-hyoscyamine) and l-hyoscyamine. Antiserum was obtained from rabbits immunized with an immunogen prepared by coupling l-hyoscyamine to human serum albumin. By using 3H-atropine as tracer, the assay can detect atropine and l-hyoscyamine concentratins down to 9 nmol/l(2.5 ng/ml) in a 0.1 ml serum or plasma sample. The recovery of atropine was near 100% when the drug was added at different concentrations to normal, pooled human plasma. Atropine and l-hyoscyamine are recognized equally well by the antibodies, but some other structurally related drugs (homatropine scopolamine) and atropine hydrolysis products (tropine, tropic acid) do not interfere. The usefulness of the method in pharmacokinetic studies was shown by assaying atropine concentrations in serial serum samples from two patients, who were given 1.3 mg atropine on connection with anaesthesia. A biexponential serum decay curve was demonstrated in both cases with a very rapid distribution phase (t 1/2 0.63 and 1.38 min.) and a much slower elimination phase (t 1/2 1.86 and 2.09 hrs.).
Topics: Adult; Animals; Atropine; Female; Half-Life; Humans; Kinetics; Rabbits; Radioimmunoassay; Stereoisomerism
PubMed: 7446137
DOI: 10.1111/j.1600-0773.1980.tb01561.x -
Journal of Applied Physiology... Aug 1986The purpose of this study was to test the hypothesis that muscarinic cholinergic receptors are involved in the initial vasodilation in red muscle vascular beds of...
The purpose of this study was to test the hypothesis that muscarinic cholinergic receptors are involved in the initial vasodilation in red muscle vascular beds of conscious rats performing slow locomotory exercise. Atropine sulfate (1 mg/kg, ia) was administered to one group of rats in which distribution of cardiac output was estimated with radiolabeled microspheres immediately before exercise while the animals were standing on the treadmill and at 30 s and 5 min of treadmill walking at 15 m/min. Blood flows within and among muscles in the atropine-treated animals were compared with flows in control rats that were given a sham injection of an equal volume of physiological saline. Heart rates were elevated above those of control animals in the atropinized rats during preexercise (+17%) and at 30 s of exercise (+15%). However, distributions and magnitudes of blood flows in nonmuscular tissues and within and among skeletal muscles were the same (P greater than 0.05) in atropinized and control rats during preexercise and at both exercise times, indicating that atropine had no effect on the distribution of cardiac output in the rats. It is concluded that muscarinic cholinergic receptors do not play a significant role in elevating muscle blood flow in conscious rats, either during the preexercise anticipatory phase or during slow locomotory exercise.
Topics: Animals; Atropine; Consciousness; Heart Rate; Hindlimb; Hyperemia; Male; Muscles; Physical Exertion; Rats; Rats, Inbred Strains; Regional Blood Flow
PubMed: 3745060
DOI: 10.1152/jappl.1986.61.2.679 -
Journal of Clinical Pharmacology Oct 1982The pharmacokinetics of atropine (dl-hyoscyamine) was studied in six normal volunteers following a single 1-mg intravenous dose of atropine. Atropine plasma levels were...
The pharmacokinetics of atropine (dl-hyoscyamine) was studied in six normal volunteers following a single 1-mg intravenous dose of atropine. Atropine plasma levels were collected for 24 hours and analyzed by radioimmunoassay. Pulse rates were monitored and compared with predose values in each subject. Atropine plasma concentrations were fitted by least-squares regression analysis. The observed maximal increase in pulse rate, at 12 to 16 minutes after the dose, correlated with the maximum predicted tissue levels of atropine based on the computer fit of the plasma atropine concentration-time data. No correlation between the time of maximum response and atropine plasma concentrations was observed. The average half-life of atropine was 4.125 hours. This data may be used to design a multiple-dosing regimen for intravenous atropine in patients.
Topics: Adult; Atropine; Humans; Injections, Intravenous; Kinetics; Male; Pulse; Radioimmunoassay
PubMed: 7174856
DOI: 10.1002/j.1552-4604.1982.tb02638.x -
British Journal of Anaesthesia May 1959
Topics: Atropine; Belladonna Alkaloids; Butylscopolammonium Bromide; Humans; Hydrocarbons, Brominated; Hyoscyamine; Oxyphenonium; Parasympatholytics; Salivary Glands; Scopolamine Derivatives
PubMed: 13662482
DOI: 10.1093/bja/31.5.205